U.S. flag

An official website of the United States government

NM_000251.3(MSH2):c.1387-9T>A AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:
Likely pathogenic (2 submissions)
Last evaluated:
May 29, 2024
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000509472.2

Allele description [Variation Report for NM_000251.3(MSH2):c.1387-9T>A]

NM_000251.3(MSH2):c.1387-9T>A

Gene:
MSH2:mutS homolog 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2p21
Genomic location:
Preferred name:
NM_000251.3(MSH2):c.1387-9T>A
HGVS:
  • NC_000002.12:g.47463022T>A
  • NG_007110.2:g.64899T>A
  • NM_000251.3:c.1387-9T>AMANE SELECT
  • NM_001258281.1:c.1189-9T>A
  • LRG_218t1:c.1387-9T>A
  • LRG_218:g.64899T>A
  • NC_000002.11:g.47690161T>A
  • NM_000251.1:c.1387-9T>A
  • NM_000251.2:c.1387-9T>A
Links:
dbSNP: rs587779087
NCBI 1000 Genomes Browser:
rs587779087
Molecular consequence:
  • NM_000251.3:c.1387-9T>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001258281.1:c.1189-9T>A - intron variant - [Sequence Ontology: SO:0001627]
Observations:
3

Condition(s)

Name:
Hereditary nonpolyposis colorectal neoplasms
Identifiers:
MeSH: D003123; MedGen: C0009405

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000607327GenomeConnect, ClinGen
no classification provided
not providedunknownphenotyping only

SCV001553258Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR)

See additional submitters

no assertion criteria provided
Likely pathogenic
(May 29, 2024) 		unknownclinical testing

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownunknownnot providednot providednot providednot providednot providedphenotyping only
not providedunknownyes3not providednot providednot providednot providedclinical testing

Details of each submission

From GenomeConnect, ClinGen, SCV000607327.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedphenotyping onlynot provided

Description

GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providedvalidationnot providednot providednot providednot provided

From Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV001553258.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided3not providednot providedclinical testingnot provided

Description

The MSH2 c.1387-9T>A variant was not in the literature. The c.1387-9T>A variant was identified in dbSNP (ID: rs587779087) and ClinVar (classified as pathogenic in association with Hereditary nonpolyposis colorectal neoplasms and Lynch syndrome 1). The variant was not identified in the following control databases: the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project, or the Genome Aggregation Database (November 01, 2023, v4.0). The c.1387-9T>A variant is located in the 3' splice region but does not affect the invariant -1 and -2 positions. However, positions -3 and -5 to -12 are part of the splicing consensus sequence and variants involving these positions sometimes affect splicing. The variant occurs inside of the splicing consensus sequence and in silico or computational prediction software programs (Splice AI exome) predict a deleterious effect on splicing. However, this information is not predictive enough to assume pathogenicity. The c.1387-9T>A variant was identified in an individual from our laboratory with a diagnosis of HNPCC. This intronic substitution was examined by RT-PCR analysis and found to cause an alternate transcript that was predicted to result in a frameshift and to create a premature stop codon. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more pathogenic role for this variant. This variant is classified as likely pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownyesnot providednot providednot provided3not providednot providednot provided

Last Updated: Oct 20, 2024